Sialic acid, a generic term for the acyl derivatives of neuraminic acid, occurs naturally in the form of a wide variety of derivatives, of which N-acetylneuraminic acid (Neu5Ac) is the most common.
In recent years, sialic acid has been found to act as a virus receptor and mediate various physiological actions such as cell recognition, cholera toxin neutralization, suppression of infection with pathogenic Escherichia coli, expectorant action and control of the hematologic half-life of blood proteins. With the increasing attention to sialic acid along with understanding of its biological roles, there have been increasing demands for its application to pharmaceuticals; for example, its supply in large amounts is strongly desired.
Although sialic acid occurs widely naturally in the non-reduced terminals of glycoproteins and glycolipids in vivo, it is difficult to produce sialic acid from a natural substance containing it both in a large amount and at a low cost and to purify it both on an industrial scale and to a high purity.
Reported methods for production of sialic acid include the method disclosed in Japanese Patent Laid-Open No. 34995/1989, in which sialic acid is produced from chick meconium, and the method disclosed in Japanese Patent Examined Publication No. 16042/1968, in which sialic acid is produced from chalaza and ovomucin obtained from chicken egg white, but none of these methods permits production of sialic acid both on an industrially large scale and at a low cost, since there is no system for industrial supply of the starting materials.
On the other hand, it is a known fact that sialic acid is present in egg yolk. However, egg yolk is used as nothing other than a raw material for mayonnaise, cakes and other foods. Industrial utilization of its components is limited to the use of egg yolk lipid as materials for cosmetics, pharmaceuticals and some foods; no one has ever attempted to industrially separate sialic acid from egg yolk.
This is because egg yolk has drawbacks in that the production process for sialic acid becomes troublesome and the cost is not favorable, since a large amount of lipid contained in egg yolk strongly emulsifies the egg yolk solution after hydrolysis in separating sialic acid from egg yolk, which in turn significantly hampers the purification process which follows.
As for a method for purification of sialic acid, Japanese Patent Laid-Open No. 34995/1989 discloses the method in which the starting material chick meconium is hydrolyzed and then adsorbed to anion exchange resin without being preceded by desalting, after which it is desalted. However, when this method is applied to production of sialic acid from delipidated egg yolk, it poses a problem, i.e., both the percent yield and purity of sialic acid are low so that high purity sialic acid cannot be industrially favorably obtained. Also, Japanese Patent Laid-Open No. 40491/1989 states that sialic acid can be purified by hydrolyzing a milk substance such as cow's milk, defatted milk, butter milk or whey, desalting the resulting hydrolyzate by electrodialysis and subsequently performing electrodialysis again. However, this method poses problems of decreased percent yield of sialic acid due to its loss during desalting and decreased purity of sialic acid due to the presence of salt impurities during purification as a result of the incapability of complete desalting.